2-(n-2-cyanoethyldithiocarbamylmethylene)-5-hydroxy-4h-pyran-4-one and metal chelates

ABSTRACT

2 - (N - 2 - CYANOETYLDITHLIOCARBAMYLMETHYLENE) - 5 HYDROXY-4H-PYRAN-4-ONE AND METAL CHELATES THEREOF ARE EFFECTIVE AGENTS FOR CONTROLLING UNDESIRABLE MICROORGANISMS.

United States Patent O 3,799,945 2-(N-2-CYANOETHYLDITHIOCARBAMYLMETHYL-ENE)-5-HYDROXY 4H PYRAN 4-0NE AND METAL CHELATES John Joseph DAmico,Akron, Ohio, assignor to Monsanto Company, St. Louis, M0. N Drawing.Filed Feb. 22, 1972, Ser. No. 228,368 Int. Cl. C07d 7/16 US. Cl.260345.9 8 Claims ABSTRACT OF THE DISCLOSURE 2 (N 2cyano'ethyldithiocarbamylmethylene) hydr0xy-4H-pyran-4-one and metalchelates thereof are effective agents for controlling undesirablemicroorganisms.

This invention relates to cyanoethyldithiocarbamic acid derivatives ofkojic acid which are toxic toward microorganisms and are particularlyvaluable for controlling Venturia inaequalis, the pathogen responsiblefor apple scab disease. Chloroalkenyl esters of cyanoethyldithiocarbamicacid have been described by DAmico as useful agents for the control offungi, U.S. 3,284,287. tApplicant herein combines thecyanoethyldithiocarbarnyl moiety with the kojic acid moiety to form newcompounds which exhibit excellent fungicidal activity.

SUMMARY OF THE INVENTION 2 (N 2 cyanoethyldithiocarbamylmethylene) 5-hydroxy-4H-pyran-4-one and its metal chelates are potent agents for thecontrol of fungi and bacteria. The new toxicants are valuable forcontrolling organisms on living plants because they exhibit fungicidaland bactericidal properties at low concentrations but are devoid ofphytotoxic properties even at higher concentrations.

The subject compound is prepared by reaction of the ammonium salt of2-cyanoethyldithiocarbamic acid andZ-(chloromethyl)-5-hydroxy-4H-pyran-4-one. The chemical formula for thecompound is I OH N C CHgCHzNH C (S) SClhio The metal chelates areprepared by complexing a metal salt with the 2-(N 2cyanoethyldithiocarbamylmethylene)-5-hydroxy-4H-pyran 4 one. Examples ofsuitable metals from which chelates may be prepared are chromium,manganese, iron, cobalt, nickel, copper, zinc, cadmium, lead and mercurywith the metals of atomic numbers of 26-30 being preferred. The chelatesare recovered as hydrates with the following postulated structure CHIS(S) CNHCHzCHa (IN-(H2O):

in which M is a metal ion and x is variable but generally is between 2-6with x being about four when the chelates are dried at 45 C. overnight.

The new toxicants are effective bactericides and fungicides and may beapplied to the habitat of the pathogen to prevent its growth and spread.The bactericidal or fungicidal compositions containing the toxicant areapplied to the area to be protected. If the area is already infected,the toxicant kills or inhibits further growth of the pathogen. If thetreated area is pathogen-free, the toxicant keeps the area sterile byinhibiting growth of 3 ,799,945 Patented Mar. 26, 1974 "ice any pathogenwhich may invade the area. The term habitat is used in its ordinarydictionary sense meaning the place where the pathogen normally lives andgrows. Typical habitats are warm, damp places, for example, locker-roomfloors or in the case of plant pathogens, the habitat is the foliage ofthe plant.

Fungicidal compositions are prepared by combining one of the abovedescribed toxicants with a liquid or solid carrier. The chelates areinsoluble in water and organic solvents and the2-(N-2-cyanoethyldithiocarbamyldithiomethylene)- 5 -hydroxy 4H pyran 4one is insoluble in water but is soluble in certain organic solvents,for example, acetone and dimethyl formamide. Aqueous dispersions of thetoxicants may be prepared to form concentrates which may be diluted withwater to form a spray suitable for application to the area to beprotected. It is recommended that a dispersing agent be used tofacilitate the formation of a more stable emulsion. The toxicants mayalso be blended with an inert solid diluent such as talc, diatomaceousearth, fullers earth, etc., to form dry compositions which are dispersedin an aqueous medium to form a liquid spray. In general, any of theconvenitional formulation and application techniques are applicable withthe subject toxicants and includes combinations with the many knownWetting agents and inert carriers and includes combinations with otherfunctional biological agents such as herbicides and insecticides.

The concentration of toxicant used varies depending upon the particularpathogen which the treatment is intended to control. Amounts of onepercent to one part per million are effective with dosages of aboutp.p.m. being generally used. Of course, it is understood that greater orlesser amounts may be used and that the invention applies to anyconcentration at which toxic effects or inhibition of the bacteria orfungi is obtained.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Example 1 To a solution of 21g. (0.3 mole) of 2-cyanoethylamine and 18.9 g. (0.3 mole) ofconcentrated ammonium hydroxide in 300 ml. of ethanol, there is addeddropwise at 5-10 C., 22.8 g. (0.3 mole) of carbon disulfide. Afterstirring the mixture for one hour at 25-30 C., 48.2 g. (0.3 mole) ofchloromethyl kojic acid is added in one portion. Upon the addition, thetemperature rises to 58 C. and precipitate forms. After stirring themixture at room temperature for 24 hours, 750 ml. of water is added andthe mixture stirred for an additional half hour. The precipitate isrecovered by filtration, washed with water until neutral to litmus andair dried at 2530 C. 2-(N-2-cyanoethyldithiocarbamylmethylene)-5hydroxy- 4H-pyran-4-one is recovered in 89% yield. The productrecrystallized from acetone melts at -166 C. Analysis gives 10.42% N and24.19% S compared to 10.36% N and 23.72% S calculated for C H N O SExample 2 The zinc chelate is prepared by adding at room temperature 4.5g. (0.031 mole) of zinc chloride in 200 ml. of water to a solutioncontaining 16 g. (0.0619 mole) of2-(N-2-cyanoethyldithiocarbamylmethylene)-5 hydroxy- 4H-pyran-4-one and10.9 g. (0.0619 mole) of 25% sodium hydroxide in 400 ml. of water. Afterstirring two hours, the precipitate is recovered by filtration, Washedwith water until neutral and air dried at 45 C. The zinc chelate of2-(N-2 cyanoethyldithiocarbamylmethylene)- 5-hydroxy-4H-pyran-4-one isrecovered in 100% yield (18 g.). Analysis gives low values for nitrogenprobably because of interference of the metal ion and 19.56% S comparedto 18.85% S calculated for By the procedure of Example 2, coppersulfate, nickel chloride, and cadmium sulfate are reacted to give therespective metal chelates. Analyses give 19.35% S compared to Scalculated for c2QH1BN406S4Cu'4I I20; 18.61% S compared to 19.03% Scalculated for and 18.15% S compared to 17.63% S calculated for C2oH1N4O S4Cd 41 1 0.

To illustrate control of bacteria and fungi, a 1.0% stock solution oremulsion of the test material is prepared in a nontoxic solvent anddiluted in agar to provide samples containing various concentrations ofthe test material. Petri dishes are respectively filled with the testmixture and the plates thus prepared inoculated with the test organism.After a suitable incubation period, the plates are inspected and theconcentration is recorded at which complete inhibition of the growth ofthe organism is obtained. Identical agar test plates with no testmaterial present show normal uninhibited growth.

At test concentrations of 100 ppm. ($5 2-(N-2-cyanoethyldithiocarbamylmethylene) hydroxy 4H- pyran-4-one and the Zn,Cu, Ni and Cd chelates thereof completely inhibit the growth of S.aureus, S. typhosa, Ps. aeruginosa, and A. niger.

In one embodiment of the invention2-(N-2-cyanoethyldithiocarbamylrn'ethylene) 5 hydroxy 4H-pyran- 4-one isapplied to foliage of apple seedlings. Plants are selected foruniformity, sprayed with the toxicant and placed on carts to dry.Twenty-four hours later a spore suspension of Venturia inaequalisconidia is made and adjusted to a concentration of approximately2,500,000 spores per ml. of water. The spore suspension is sprayeduniformly over the foliage of the treated and untreated trees.Immediately thereafter the plants are placed into the incubation chamber(100% relative humidity). Seventy-two hours later the trees are removedand after a drying period are placed on greenhouse benches. Two weekslater apple scab tests are evaluated. The test consists of counting thenumber of parasitized leaves on each plant (3 replicates per treatment),determining the average number of parasitized leaves per tree for agiven treatment, and expressing the result as percent control. Thepercent control for each treatment is found by dividing the averagenumber of parasitized leaves per tree in the untreated specimens intothe average number of parasitized leaves per tree in the treatedspecimens, multiplying this number by 100 and subtracting it from 100.Comparisons are made with the commerical fungicide N-trichloromethylthiotetrahydropthalimide (Captan). The percent control based on untreatedtrees (average of three) at various concentrations is shown in thefollowing table.

The data show the toxicant of this invention is highly effective forcontrolling apple scab disease. No herbicidal effect upon the appletrees is observed even at the highest test concentration. In regard tophytotoxicity, at rates of 10 pounds per acre the toxicants of theexamples exhibit essentially no phytotoxic properties against a spectraof broadand narrow-leafed plants.

In another embodiment of the invention,2-(N-2-cyanoethyldithiocarbamylmethylene) 5 hydroxy-4H-pyran- 4-one isapplied to foliage of tomato plants. The procedure is essentially thesame as described above for the apple tree tests except the treated anduntreated plants are sprayed with a suspension of Phytophthora infestansthe pathogen which causes the disease commonly called late blight.Comparisons are made with the commercial fungicide manganese ethylenebisdithiocarbamate (Maneb). The percent control based on untreated tomatoplants at various concentrations is shown in the following table.

Percent Control of Late Blight The data show that the toxicant of thisinvention is more effective at low concentrations than the commercialfungicide. No phytotoxic effects due to the toxicant is observed.Similar tests with the chelates of this invention give substantially thesame degree of control of apple scab and late blight.

Although the invention has been illustrated by typical examples, it isnot limited thereto. Changes and modifications of the examples of theinvention herein chosen for purposes of disclosure can be made which donot constitute departure from the spirit and scope of the invention.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:

1. 2 (N 2 cyanoethyldithiocarbamylmethylene)- 5-hydroxy-4H-pyran-4-oneand metal chelates thereof.

2. The compound of claim 1, 2-(N-2-cyanoethyldithiocarbamylmethylene) -5-hydroxy-4H-pyran-4-one.

3. The metal chelate of claim 1 in which the metal is selected from thegroup consisting of chromium, manganese, iron, cobalt, nickel, copper,zinc, cadmium, lead and mercury.

4. The metal chelate of claim 3 in which the metal has an atomic numberof 26 to 30.

5. The metal chelate of claim 3 in which the metal is 6. The metalchelate of claim 3 in which the metal is copper.

7. The metal chelate of claim 3 in which the metal is nickel.

8. The metal chelate of claim 3 in which the metal is cadmium.

No references cited.

NORMA S. MILESTONE, Primary Examiner US. Cl. X.R. 424245, 283

